Phosphorylation of Fanconi anemia protein, FANCA, is regulated by Akt kinase.
Phosphorylation of the Fanconi anemia complementation group A (FANCA) protein is thought to be important for the function of the FA pathway. However, the kinase for FANCA (so-called FANCA-PK) remains to be identified. FANCA has a consensus sequence for Akt kinase near serine 1149 (Ser1149), suggesting that Akt can phosphorylate FANCA. We performed in vitro kinase assays using as substrate either a GST-fusion wild-type (WT) FANCA fragment or a GST-fusion FANCA fragment containing a mutation from serine to alanine at 1149 (FANCA-S1149A). These experiments confirmed that FANCA is phosphorylated at Ser 1149, in vitro. However, (32)P-orthophosphate labeling experiments revealed that FANCA-S1149A was more efficiently phosphorylated than WT-FANCA. Furthermore, phosphorylation of wild-type FANCA was blocked by coexpression of a constitutively active (CA)-Akt and enhanced by a dominant-negative (DN) Akt. Our results suggest that Akt is a negative regulator of FANCA phosphorylation.
Pubmed ID: 11855836 RIS Download
Amino Acid Sequence | Cell Line | Consensus Sequence | DNA-Binding Proteins | Fanconi Anemia Complementation Group A Protein | Genetic Complementation Test | Humans | Phosphorylation | Precipitin Tests | Protein-Serine-Threonine Kinases | Proteins | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-akt